It is often essential to characterize particles by their size, as well as their ability to bind to other particles or molecules. When the particles are biological particles, the information gained about their ability to bind, or not to bind, to certain particles or molecules can provide useful information. Additionally, it is useful in certain diagnostic applications to detect known changes of the surface of a biological particle. Accordingly, it can be desirable to detect the surface chemistry and monitor changes to the surface chemistry in an efficient and accurate manner.
“Electrophoretic Quasi-Elastic Light Scattering” (EQELS) is one method for characterizing biological particles. This method uses electrophoresis that is dependent on the particle's surface charge density to identify and characterize suspended biological particles. EQELS uses cells placed in an electric field, where the surface charge of the particle will determine how that particle moves in the electric field. Monitoring the electrophoretic mobility of the cells provides information useful in distinguishing among different particles in the field. One can screen and optimize drug candidates which interact with the biological particles by comparing the spectra of the particles alone, or particles bound to the drug candidates.
Coulter counters can also be used to characterize biological particles. These devices are used primarily to count and size cells and other biological particles. The Coulter Counter works by drawing fluid containing the biological particle through a small opening located within a current between two electrodes, and detecting the change in electric conductance. As the fluid is drawn through the opening, the biological particles flow through the current and measurably disturb a portion of the current. The measurable displacement is translated to a pulse that is digitally processed by the Coulter Counter and translated to allow one to characterize the size and number of biological particles in the fluid.
Flow cytometry can also be used to characterize biological particles. Flow cytometry uses a beam of light, such as a laser, trained on a fluid to characterize, count and optionally sort particles in the fluid. The fluid is focused into a stream, and detectors near to the intersection of the light and the fluid stream determine light scatter—both forward and side. Additionally, one or more fluorescent detectors may be present to detect fluorescent or fluorescently-tagged particles. One can determine various physical and chemical characteristics of each individual particle by analyzing the detected pattern.
These methods are useful in detecting and characterizing microparticles, including determining the number of particles, number density within a fluid medium, size, and surface characteristics of the particle, confirming binding, or lack thereof, and the like. The particles are generally in the size of between 0.1 μm and 50 μm. However, each of these methods has various limitations, including the speed in which the assays can be performed, the size of particles that can be measured, and the like.
There remains a need for additional devices and processes for characterizing particles, including biological particles, which can detect particles with accuracy, quantify the particles and/or determine whether one or more of the particles bind to other particles or molecules. The present invention provides such devices and processes.